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Biomedical subjects

M Ernst

Publications and source records attributed to M Ernst.

At least 109 records · Page 6Linked to original sources
PubMed1998

Health hazards of radiation exposure in the context of brain imaging research: special consideration for children.

UNLABELLED: This review provides information on health and biological effects of low-dose radiation to help institutional review boards and investigators make educated assessments of the risks of low-level radiation exposure involved in research, particularly in children. METHODS: Studies of low-level radiation exposure with large sample sizes and long follow-up were reviewed. To help interpret the studies, we clarified the measures and measurement strategies of radiation exposure and of health risks. The few large studies of risks of low-level radiation in children have failed to detect an increased incidence of cancer. Most studies of low-level radiation involve adults. RESULTS: The risk of increased rates of cancer after low-level radiation exposure is not supported by population studies of health hazards from exposure to background radiation, radon in homes, radiation in the workplace or radiotherapy. Compared to the frequency of daily spontaneous genetic mutations, the biological effect of low-level radiation at the cellular level seems extremely low. Furthermore, the potentiation of cellular repair mechanisms by low-level radiation may result in a protective effect from subsequent high-level radiation. Studies approved by institutional review boards in the U.S. that involve the exposure of healthy normal children to ionizing radiation were reviewed. CONCLUSION: Health risks from low-level radiation could not be detected above the "noise" of adverse events of everyday life. In addition, no data were found that demonstrated higher risks with younger age at low-level radiation exposure.

Brain↗
PubMed1998

Apoptosis in monocytes.

Apoptosis is a major mechanism for reducing acute inflammation by elimination of unwanted cellular responses causing tissue damage and monocytes (Mo) and macrophages (Mo) play an important role in these processes. Therefore, in the following we summarize how these cells may contribute to regulation of apoptosis of other cells and discuss the factors involved.

Animals↗
PubMed1997

Distinct roles for leukemia inhibitory factor receptor alpha-chain and gp130 in cell type-specific signal transduction.

Leukemia inhibitory factor (LIF) induces a variety of disparate biological responses in different cell types. These responses are thought to be mediated through the functional LIF receptor (LIFR), consisting of a heterodimeric complex of LIFR alpha-chain (LIFRalpha) and gp130. The present study investigated the relative capacity of the cytoplasmic domains of each receptor subunit to signal particular responses in several cell types. To monitor the signaling potential of LIFRalpha and gp130 individually, we constructed chimeric receptors by linking the extracellular domain of granulocyte colony-stimulating factor receptor (GCSFR) to the transmembrane and cytoplasmic regions of either LIFRalpha or gp130. Both chimeric receptors and the full-length GCSFR in expressed in M1 myeloid leukemic cells to measure differentiation induction, in embryonic stem cells to measure differentiation inhibition, and in Ba/F3 cells to measure cell proliferation. Our results demonstrated that whereas GCSFR-gp130 receptor homodimer mediated a GCSF-induced signal in all three cell types, the GCSFR-LIFRalpha receptor homodimer was only functional in embryonic stem cells. These findings suggest that the signaling potential of gp130 and LIFRalpha cytoplasmic domains may differ depending upon the tissue and cellular response initiated.

Antigens, CD↗
PubMed1997

An Fc gamma receptor I (CD64)-negative subpopulation of human peripheral blood monocytes is resistant to killing by antigen-activated CD4-positive cytotoxic T cells.

It has been demonstrated that in monocyte/T cell co-cultures activated with recall antigens, cytotoxic T cells were generated which are able to reduce the number of antigen-presenting monocytes. In previous studies we could show that a minor subset of monocytes, the Fc gamma receptor I-negative (CD64-) monocytes, exhibits significantly higher antigen-presenting capacity than the main population of monocytes (> 90%) which are Fc gamma receptor I-positive (CD64+). Therefore, we addressed the question whether they are also differentially susceptible to T cell-mediated killing. In the present study we demonstrate that the CD64- monocyte subset is more resistant to killing by antigen-activated T cells than CD64+ monocytes, as indicated by a higher viability and recovery of CD64- monocytes. This mechanism involves CD95 (Fas) antigen, since monocyte death in co-cultures with antigen-activated T cells could be partially reduced by blocking anti-Fas monoclonal antibodies (mAb). In agreement with this finding, although CD95 antigen was expressed on CD64+ and CD64- monocytes at comparable levels, killing of CD64- monocytes by activating anti-Fas mAb was lower than of CD64+ monocytes.

CD4-Positive T-Lymphocytes↗
PubMed1997

Relationship of polymorphisms in the renin-angiotensin system and in E-selectin of patients with early severe coronary heart disease.

Previous association studies between angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) polymorphisms and several cardiovascular diseases have reported variable results. Therefore we examined the association of the DNA variants of ACE and AGT with early, severe coronary heart disease (CHD). In addition, we compared the genotypes of both polymorphisms and the recently discovered polymorphism in the E-selectin gene in both patients and an unselected population. This study included 113 patients with severe CHD (50 years old or less) and up to 197 control subjects. The frequencies of the ACE I/D variants were 48% I and 52% D in the controls and 46% I and 54% D in the patients. The frequencies of the AGT-M235T polymorphism were 60.8% M and 39.2% T in controls and 49.1% M and 50.9% T in the patients. The frequencies of the S128R polymorphism of the E-selectin were 91.3% S and 8.7% R in controls and 84.5% S and 15.5% R in the patients. In our studies the DD genotype of ACE was not associated with early severe CHD. We found a correlation between the M235T molecular variant of AGT and the S128R variant of E-selectin to early severe CHD.

Adult↗
PubMed1997

Effects of colony-stimulating factors on cellular cytotoxicity.

Colony-stimulating factors (CSF) are used clinically in the treatment of chemotherapy-induced myelosuppression and in support of bone marrow transplantation. As CSF are known to have pleiotropic functions, their effects on cellular cytotoxicity were analysed in vitro against bladder carcinoma cell lines. By means of an L-[3H]methionine-release assay, the cytotoxicity of peripheral blood mononuclear cells against the natural-killer(NK)-cell-resistant bladder carcinoma cell lines BT-A and SBC-7 was measured using different effector/target-cell ratios. Costimulatory effects of granulocyte-colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and stem cell factor (SCF) on the generation of lymphokine-activated killer (LAK), bacillus Calmette-Guérin-activated killer (BAK) and natural killer (NK) cell cytotoxicity were investigated in this assay. Furthermore, the effect of CSF on proliferation of urothelial tumor cells in vitro was determined by a [3H]thymidine DNA-labelling technique. GM-CSF, but not G-CSF, IL-3 or SCF, was able to increase NK, BAK and LAK cytotoxicity in a dose-dependent manner. No acceleration of carcinoma cell proliferation was evident under the conditions of our assay. These data indicate the costimulatory effect of GM-CSF on cellular cytotoxicity, which might be used for immunotherapeutic purposes.

Cell Division↗
PubMed1997

Selegiline in ADHD adults: plasma monoamines and monoamine metabolites.

Plasma monoamines and monoamine metabolites were assessed before and during selegiline treatment in adults with attention deficit/hyperactivity disorder (ADHD). Selegiline, at low dose, is a selective monoamine oxidase inhibitor type B (MAOI-B). After 2-week placebo baseline, 36 ADHD adults were randomized to 6-week placebo or 20 mg/day or 60 mg/day selegiline, followed by 2-week posttreatment placebo. Twenty-seven subjects continued into a 6-week 20-mg/day or 60-mg/day selegiline period. Behavioral variables included self-rated scores on the Conners' Abbreviated Teacher Rating Scale (Conners-ATRS) and performance on a Continuous Performance Task (CPT). Plasma samples were assayed for amines (dopamine, norepinephrine, epinephrine), precursor (DOPA), and metabolites (HVA, DOPAC, DHPG, normetanephrine, metanephrine, 5-HIAA). Selegiline produced dose-dependent changes in monoamine metabolites and DOPA plasma levels. Dopaminergic indices were associated with ADHD symptom severity (Conners-ATRS) and noradrenergic indices with CPT performance. Serotonergic metabolism, challenged by selegiline, correlated with clinical changes. These findings support a multisystem dysfunction underlying ADHD pathophysiology.

Adult↗
PubMed1997

Intravenous dextroamphetamine and brain glucose metabolism.

This study reports the effects of intravenous dextroamphetamine on cerebral glucose metabolism assayed by positron emission tomography (PET) and [fluorine-18]fluorodeoxyglucose (FDG) in 13 healthy adults during the performance of a continuous visual attention task. Two FDG PET scans were performed within a single experimental session. The first scan was preceded by the injection of placebo and the second scan by the injection of 0.15 mg/kg dextroamphetamine. Global and normalized regional glucose metabolic rates (rCMRglc) were examined as a function of pharmacological challenge and subjective experience. Subcortical, limbic, frontal, and cerebellar rCMRglc significantly increased after dextroamphetamine, whereas rCMRglc of the temporal cortex significantly decreased. Physiological and self-report measures of subjective states showed the expected alterations. These rCMRglc changes reflect both the direct pharmacological effect of dextroamphetamine on monoaminergic neurotransmitter systems as well as enhancement of the activation of the neural network mediating the performance of the continuous attention task.

Adult↗
PubMed1997

Use of propofol anesthesia during outpatient radiographic imaging studies in patients with Lesch-Nyhan syndrome.

Lesch-Nyhan syndrome is a rare, x-linked, recessive disorder of purine metabolism resulting in hyperuricemia, spasticity, choreoathetosis, dystonia, self-injurious behavior, and aggression, without significant cognitive impairment. Anesthetic management of inpatients who demonstrate classic manifestations of Lesch-Nyhan syndrome and require surgical interventions have been described. There are no guidelines in the literature addressing the anesthetic management of the outpatient with Lesch-Nyhan syndrome. Specifically, sudden, unexplained death, abnormalities in respiration, apnea, severe bradycardia, and an increased incidence of vomiting and chronic pulmonary aspiration may preclude this patient population from receiving anesthesia for outpatient procedures. General anesthesia with spontaneous ventilation was performed for diagnostic, radiographic imaging in 11 outpatients with Lesch-Nyhan syndrome using intravenous propofol. A bolus dose of 1.5 to 2.0 mg/kg propofol was followed by maintenance doses of 60 to 160 mcg/kg/min. Results during and following sedation indicated end-tidal carbon dioxide ranges between 34 mmHg and 59 mmHg. Respiratory rates were never below 10 breaths/min and no partial/complete airway obstruction or labored breathing was clinically evident. Hemodynamics were within 30% of presedation values. No patient demonstrated nausea, vomiting, or pulmonary aspiration. Baseline neuropsychologic status was achieved following sedation, and patients were discharged from the hospital 35 to 90 minutes after sedation was completed. Potential risks and benefits of using propofol in this patient population are discussed.

Adolescent↗
PubMed1997

Flow cytometric investigation of non-specific erythrocyte antigens.

Thirteen monoclonal antibodies submitted to the Third Workshop on Erythrocyte Antigens from the panel "non-specific erythrocyte antigens" were tested for their reactivity with different types of cells. Most of them were defined as specific for adhesion antigens. The CD 44 antibodies 2D3-1, 2D3-2, 2D3-3 and 2D3-4 reacted as expected for CD 44 except their negative reactivity with the myeloid cell line HL 60 and B-cell line Raji. The CD 47 antibodies 2D3-5 and 2D3-6 reacted specific. Only with Raji and T-cell line MOLT 4 the CD 58 antibodies 2D3-7 and 2D3-8 showed reactivity as expected which indicates that they are "CD 58 related". The CD 99 antibody 2D3-9 shows similar results as expected for a CD 99 specific antibody except its high reactivity against Raji. From the RBC-related antibodies 2D3-11 and 2D3-12 the latter becomes completely negative with trypsin treated erythrocytes. The antibody is negative on normal peripheral blood lymphocytes but reacts with transformed cell lines like Raji and MOLT 4. With a view to their reactivity to the cells tested at least 2D3-13 of the Rh-related antibodies seems to be similar to CD 47 antibodies.

12E7 Antigen↗
PubMed1997

Isolation and characterization of a leukemia inhibitory factor-independent embryonic stem cell line.

Leukemia inhibitory factor (LIF) is a mammalian cytokine that has a wide range of physiological activities, including the inhibition of differentiation of embryonic stem (ES) cells. We have used insertional mutagenesis in an attempt to isolate molecules that participate in LIF signal transduction via the LIF receptor. Using a robust screen for undifferentiated cells, we have isolated one ES cell line, Poly 27, that does not require exogenous LIF to remain undifferentiated in vitro. We present evidence that Poly 27 is not irreversibly committed to an undifferentiated phenotype, but can differentiate in vitro if cultured in the presence of chemical differentiating agents, while in syngeneic mice Poly 27 cells form tumours which are composed largely of undifferentiated cells. We have characterized the mechanism of factor independence in Poly 27, and shown it to be a result of autocrine LIF production. This LIF production is potentially the result of a mutation in a gene critically involved in regulating LIF production in ES cells.

Animals↗
PubMed1997

Cerebral glucose metabolism in adolescent girls with attention-deficit/hyperactivity disorder.

OBJECTIVE: Low cerebral metabolic rates for glucose (CMRglc) have been reported in a small sample of girls with attention-deficit/hyperactivity disorder (ADHD). This study was an effort to replicate this finding in a larger independent sample. METHOD: Using positron emission tomography and [18F]fluorodeoxyglucose, CMRglc were compared between 10 girls with ADHD (14.10 +/- 1.91 years) and 11 normal girls (14.3 +/- 1.70 years). RESULTS: Global CMRglc was similar between ADHD and control girls. Lateralization of normalized CMRglc differed significantly between ADHD and control girls in parietal and subcortical regions, with rCMRglc lower on the left than on the right side in girls with ADHD, and conversely in control girls. The sylvian area of the parietal region and the anterior putamen of the subcortical region were the main contributors to this effect. Normalized rCMRglc of the hippocampus was higher in ADHD than in control girls. Sexual maturation was the only clinical characteristic that differed between present and previous samples, and it correlated with global CMRglc. CONCLUSIONS: Although failing to confirm abnormally low CMRglc in girls with ADHD, this study suggested that (1) functional interactions between sex and brain development may contribute to ADHD pathophysiology, and (2) sexual maturation should be controlled in future CMRglc studies of adolescent girls.

Adolescent↗
PubMed1997

Follow-up of radial arterial catheterization for positron emission tomography studies.

Radial arterial catheterization is needed for repeated arterial blood samples to construct tracer input curves of positron emission tomography (PET) scans (Herscovitch [1993]: Rheum Dis Clin North Am 19:765-794). Complications resulting from such short-term catheterizations are rare. Sixteen investigators followed 106 subjects who had arterial lines placed in the context of a PET study. Abnormalities were reported in 8 of 106 (7.5%) cases. Of these eight cases, three (37.5%) were inpatients diagnosed with anorexia nervosa, a condition that may represent a risk factor. All abnormalities were benign, did not affect motor function, and did not require medical intervention.

Adult↗
PubMed1997

Accessory function of alveolar macrophages from patients with sarcoidosis and other granulomatous and nongranulomatous lung diseases.

BACKGROUND: Accessory function (AF) is one way antigen presenting cells generate sufficient secondary signals for optimal T-cell proliferation and IL-2 production. In general, alveolar macrophages (AM) are inferior accessory cells in comparison to monocytes whereas in sarcoidosis AF of AM is increased. METHODS: We compared the accessory index (AI) of AM and peripheral blood monocytes (PBM) of 41 patients with inactive sarcoidosis (SAR I, n = 12); active sarcoidosis with new or progressing symptoms (SAR II, n = 19), active sarcoidosis with spontaneous remission (SAR III, n = 10), tuberculosis (TB, n = 12), hypersensitivity pneumonitis (HP, n = 12), Wegener's disease (WD, n = 2), undefined alveolitis (UA, n = 8) and chronic obstructive pulmonary disease (COPD, n = 6) by employing the histoincompatibility-insensitive Jurkat cells as indicator cells. RESULTS: Compared with the controls (1.08 +/- 0.3) AMs of all groups but SAR I (AI: 0.96 +/- 0.42) exhibited significantly increased AIs (SAR II: 3.6 +/- 3.9; SAR III: 3.2 +/- 2.4; TB: 2.8 +/- 2.2; HP: 3 +/- 2; UA: 2.7 +/- 2.3; COPD: 3.1 +/- 2.2; p < 0.05 for all comparisons). Only in HP, AI of PBM was significantly increased compared with controls (3 +/- 1.5, 1.3 +/- 0.5, respectively; p < 0.001). Alveolar macrophages from patients with arcoidosis, TB, and HB express the costimulatory molecule CD80 on their surface and anti-CD80 antibodies inhibited the IL-2 release of Jurkat cells in this system to 59 +/- 27%. CONCLUSIONS: Our data demonstrate that AM from patients with various diseases have the capability to act as competent accessory cells and that the reported accessory function of these cells is at least in part mediated by the expression of CD80.

Adult↗
PubMed1996

Gp130-mediated signal transduction in embryonic stem cells involves activation of Jak and Ras/mitogen-activated protein kinase pathways.

The leukemia inhibitory factor/interleukin 6 (LIF/IL6) family of cytokines promotes cell type-specific pleiotropic effects by engaging multimeric receptor complexes that share the common affinity converter/signal transducing subunit gp130. While the maintenance of embryonic stem (ES) cell self-renewal is an activity unique to this family of cytokines, the intracellular signaling events mediated by gp130 remain largely unknown. Here we show a rapid and transient increase in the specific activity of the Src-related kinase Hck as well as of the Janus kinases Jak1, Jak2, and Tyk2 following treatment of ES cells with LIF or a combination of IL6 plus a soluble form of the IL6 receptor. Within 2 min of stimulation, we also observed increased tyrosine phosphorylation of SHC, activation of the guanidine nucleotide exchange activity on p21(ras), and an electrophoretic mobility shift of MAP kinase. Functional involvement of Hck and p21(ras) activation in gp130-mediated signaling is supported by the finding that the introduction of constitutively activated Hck or v-Ha-ras partially alleviates the requirement of ES cells for LIF to remain undifferentiated. In contrast, suppression of Jak1 in ES cells by antisense technology increased the amount of LIF required to retain their pluripotentiality. These results are consistent with the notion that gp130-mediated suppression of ES cell differentiation depends on signaling through at least two cascades, namely a p21(ras)-dependent pathway that possibly involves Hck, as well as a Jak kinase-dependent pathway.

Antigens, CD↗
PubMed1996

Presynaptic dopaminergic deficits in Lesch-Nyhan disease.

BACKGROUND: Lesch-Nyhan disease is a rare, devastating, X-linked recessive disorder of purine synthesis. Patients present with hyperuricemia, choreoathetosis, dystonia, and aggressive and self-injurious behavior. Although the genetic and biochemical abnormalities have been identified, the causes of the neuropsychiatric syndrome remain unclear. METHODS: We used positron-emission tomography to measure presynaptic accumulation of fluorodopa F 18 tracer in the dopaminergic regions of the brains of 12 patients with Lesch-Nyhan disease (age, 10 to 20 years) and 15 healthy controls (age, 12 to 23). The results were expressed as ratios of specific to nonspecific radioactive counts. A low ratio indicates decreased dopa decarboxylase activity and dopamine storage. RESULTS: The fluorodopa F 18 ratio was significantly lower in the putamen (31 percent of control values), caudate nucleus (39 percent), frontal cortex (44 percent), and ventral tegmental complex (substantia nigra and ventral tegmentum; 57 percent) in the patients with Lesch-Nyhan disease than in the controls. Uptake of the tracer was abnormally low even in the youngest patients tested, and there was no overlap in the values between patients and controls. CONCLUSIONS: Patients with Lesch-Nyhan disease have abnormally few dopaminergic nerve terminals and cell bodies. The abnormality involves all dopaminergic pathways and is not restricted to the basal ganglia. These dopaminergic deficits are pervasive and appear to be developmental in origin, which suggests that they contribute to the characteristic neuropsychiatric manifestations of the disease.

Adolescent↗